What is the primary treatment for hypogonadism?

Testosterone Replacement Therapy for Hypogonadism

Testosterone replacement therapy (TRT) is the primary treatment for confirmed hypogonadism in adult males with documented testosterone deficiency. 1 This treatment is specifically indicated for conditions associated with deficiency or absence of endogenous testosterone, including primary hypogonadism (testicular failure) and hypogonadotropic hypogonadism (pituitary-hypothalamic dysfunction). 2

Diagnosis Confirmation

Before initiating treatment:

• Confirm hypogonadism with morning total testosterone concentrations drawn between 8-10 AM on at least two separate days 1
• Determine if primary (testicular) or secondary (pituitary-hypothalamic) hypogonadism by measuring LH and FSH levels 1
• For secondary hypogonadism, consider additional testing including serum prolactin, iron saturation, pituitary function tests, and MRI of the sella turcica 1

Treatment Options

First-Line Options:

1. Transdermal Preparations 1

   • Gels (1% or 1.62%): Provide stable day-to-day testosterone levels with convenient application
   • Patches: Minimize transfer risk compared to gels
   • Starting dose for 1.62% gel: 40.5 mg of testosterone applied topically once daily in the morning to shoulders and upper arms 2

2. Injectable Testosterone 1, 3

   • Testosterone Enanthate/Cypionate
   • Advantages: Less frequent administration, lower cost
   • Disadvantages: Fluctuating testosterone levels, injection discomfort

Dose Adjustment and Monitoring:

• Target testosterone levels should be in the mid-normal range (450-600 ng/dL) 1
• Monitor testosterone levels 2-3 months after treatment initiation and after dose changes, then every 6-12 months once stable 1
• For injectable testosterone, measure levels midway between injections 1
• Adjust dose based on pre-dose morning testosterone levels: 1, 2

  • 750 ng/dL: Decrease daily dose by 20.25 mg

  • 350-750 ng/dL: No change
  • <350 ng/dL: Increase daily dose by 20.25 mg

Special Considerations

Fertility Preservation:

Standard TRT suppresses the hypothalamic-pituitary-gonadal axis, which can impair fertility 4. For men wishing to preserve fertility, alternative options include:

• Nasal TRT (shorter half-life with less HPG suppression)
• Selective estrogen receptor modulators (clomiphene citrate)
• Exogenous gonadotropins
• Aromatase inhibitors (though limited by risk of osteopenia) 5

Potential Adverse Effects:

• Erythrocytosis: Dose-dependent (2.8-17.9% incidence) 1
• Skin reactions: More common with patches (up to 66%) than gel (5%) 1
• Other effects: Suppression of spermatogenesis, peripheral edema, emotional lability 1
• Secondary exposure risk: Children should avoid contact with unwashed application sites 2

Contraindications:

• Prostate cancer
• Male breast cancer
• Desire for near-term fertility
• Severe sleep apnea
• Uncontrolled heart failure
• Hematocrit >54% 1

Important Clinical Considerations

• The FDA has approved testosterone only for true hypogonadism, not for "age-related hypogonadism" 1, 2
• Application site and dose of testosterone gel products are not interchangeable with other topical testosterone products 2
• Recent evidence suggests TRT may be safe in men with severe lower urinary tract symptoms and untreated obstructive sleep apnea, potentially challenging previous contraindications 6
• High-quality evidence suggests TRT does not increase stroke or heart attack risk in men 45-80 years old, even those with cardiovascular risk factors 1

TRT has demonstrated benefits including increased lean muscle mass, reduced body fat, improved sense of well-being, improved bone density, and improvements in sexual function and quality of life when used appropriately for confirmed hypogonadism 1.